Lectures 12 & 13 Flashcards
receptors and signaling (44 cards)
Many molecular processes transduce _______ signals (drug) into intracellular ______ (effect) and thus control cell function.
extracellular
messages
Intracellular receptors that regulate _______ involve a lipid-soluble ligand that crosses the cell membrane and acts on an intracellular receptor. Examples include corticosteroids, vitamin D, and thyroid hormone.
gene expression
Intracellular receptors that regulate gene expression stimulate the transcription of genes in the nucleus by binding to ________ near the gene whose expression is to be regulated.
specific DNA sequences
Drugs that effect intracellular receptors produce their effects after a _______ and cannot be expected to induce change within minutes. The effects of these agents can be persistent even after their concentration has been reduced to zero.
characteristic lag period
The persistence of drugs effecting intracellular receptors is due to the relatively slow turnover of most _____ and _______ and due to the ______ affinity of receptors for the hormone.
enzymes and proteins
high
___________ are effector enzymes that regulate cellular function including membrane potential, protein phosphorylation, translation, transcription, etc. (ex: adenylyl cyclase, phospholipase, kinases, etc.)
Non-receptor receptors
________ activation leads to activation associated tyrosine kinase molecules (JAK) and phosphorylation of signal transducers and activators of transcription (STAT).
cytokine receptors
______ is an enzyme which adds a phosphate group to a substrate.
kinase
The _________ receptor consists of an extracellular hormone-binding domain and a cytoplasmic enzyme domain.
protein tyrosine kinase
Protein tyrosine kinase receptors usually act as _____.
dimers
In PTKs, the hormone binds to the receptor’s extracellular domain and induces a __________. Receptor molecules associate, which brings together the ________. Kinase becomes capable of _________ itself. Tyrosine phosphorylation allows receptors to recruit _______, which become the signal for the effects of the ligand.
conformational change
PTK domains
phosphorylating
proteins
How might you turn off the protein tyrosine kinase process?
The duration and intensity of the action is limited by receptor down regulation. Upon ligand binding, endocytosis of the receptor is stimulated
Therefore, the receptor would have to be internalized so that the receptor cannon bind extracellularly.
Many drugs modulate ________ that regulate the flow of ions through the plasma membrane. They are involved in pain, neurotransmitter release, and epilepsy.
voltage-gated ion channels
Voltage-gated channels can be regulated by ______ and _______.
phosphorylation
G proteins
Many of the most useful drugs act by mimicking or blocking the actions of endogenous ligands that regulate the flow of ions through the plasma membrane _________. (ex: acetylcholine, excitatory amino acids)
ligand-gated channels
In ligand-gated channels, following the ligand binding, the signal is transmitted across the plasma membrane by increasing transmembrane conductance of the relevant ion, altering _______________.
electrical potential across the membrane
Time elapsed in ligand-gated channels from binding of the agonist to cellular response is often ______. This is crucially important for extremely rapid transfer of signals across synapses.
milliseconds
In GPCRs, the ligand acts by modulating effectors and/or intracellular concentrations of ________, such as cAMP, Ca2+, and phosphoinositides.
second messengers
What are the three components of GPCRs?
R: cell surface receptor, detects extracellular ligand
G: G protein, located on the inside of the cell, activated by receptor
E: effector element, usually an enzyme or an ion channel, activity changed by the activated G protein
cAMP’s effector enzyme is _______, which converts ATP to cAMO.
adenylyl cyclase
cAMP exerts many of its effects by stimulating ________.
cAMP-dependent protein kinases (PKA)
The _______ of cAMP regulatory effects resides in the distinct substrates of the kinases that are expressed in different cells and through cellular compartmentalization of signaling complexes.
specificity
Calcium and phosphoinositides effector enzyme is _______, which will result in the release of phosphoinositides and diacylglycerol.
phospholipase C (PLC)
Phosphoinositides result in the release of ______.
calcium
